Helicobacter pylori is a gram-negative bacillus with a diameter of approximately 0.5 μm and a length of 3-5 μm. Helicobacter pylori is a spiral shaped bacterium twisted 2 or 3 times, microscopically observed as an S-shaped bacterium or a winding gull wing-shaped bacterium. Helicobacter pylori has 4-8 flagella (called polar flagella) at both ends (poles) of the long axis and can swim and move in a solution or mucous by rotational movement of these flagella. Helicobacter pylori is a microaerophilic and highly-auxotrophic bacterium that is difficult to isolate and culture. Helicobacter pylori can be cultured in a specialized medium under conditions of 5% oxygen concentration and 5-10% carbon dioxide concentration.
Helicobacter pylori inhabits the stomach lining of humans Helicobacter pylori is a causative organism of gastritis, gastric ulcer, and duodenal ulcer, and is also considered to be involved in diseases, such as gastric MALT lymphoma, atrophic gastritis, and gastric hyperplastic polyp. Once Helicobacter pylori infects the gastric mucosa, it cannot be decolonized and persists in the stomach in spite of strong immunological response against the infection. In addition, very low intragastric pH due to hydrochloric acid inactivates many antibiotics.
For this reason, an antibiotic and a proton pump inhibitor that strongly inhibits gastric-acid secretion are used in combination to decolonize Helicobacter pylori. According to the revised guideline for diagnosis and treatment of Helicobacter pylori infection of the Japan Society of Helicobacter Research as of February 2003, a combination therapy with three agents (proton pump inhibitor+amoxicillin+clarithromycin) administered for one week is of first choice.
However, a very serious problem of increased resistant bacteria due to chronic administration of an antibiotic is concerned. In Japan, clarithromycin-resistant bacteria have increased rapidly since 2004, accounting for 25-30% in 2004 (according to a surveillance by the Japan Society of Helicobacter Research), and have increased further in recent years. Reportedly, in cases of infection with resistant bacteria, decolonization rates are decreased markedly and clarithromycin resistance occurs after failure of decolonization. Therefore, an easy and insufficient decolonization therapy is considered to increase the emergence of resistant bacteria. Furthermore, in cases for which a macrolide antibiotic was previously used for a long time, bacteria may have acquired drug resistance against clarithromycin (according to the above-mentioned guideline for diagnosis and treatment of Helicobacter pylori infection).
Therefore, development of decolonizing agents of Helicobacter pylori, free from these disadvantages, has been waited.